Editorial

We need access to all data from all clinical trials

Peter C Gøtzsche04 October 2011

A variety of international organisations, funders, and others have made calls for sharing research data. These include the Organisation for Economic Co-operation and Development (OECD), the World Health Organization (WHO), the US National Institutes of Health (NIH), the US Congress, the European Commission, the European Ombudsman, journal editors, the UK Medical Research Council (MRC), the Wellcome Trust, the Bill and Melinda Gates Foundation, and the Hewlett Foundation.[1]

These calls have mostly been restricted to publicly funded research, but if the over-riding objective of healthcare research is to improve patient care and health policy, the distinction between publicly funded research and industry-funded research is artificial and irrelevant.[1,2] It is pretty clear that if commercial concerns lead to the withholding of data that are important for rational decision-making by doctors and patients, there is something fundamentally wrong.

Selective reporting of trial results is common,[3-8] and this means that published results of trials – and therefore also systematic reviews of trials – tend to exaggerate the beneficial effects of healthcare interventions and underestimate their harms, often to a considerable degree. Because of selective reporting, many patients have been treated unknowingly with interventions that have no effect, and many have been harmed unnecessarily. This practice is unethical [9] and violates the implicit contract that healthcare researchers have with those members of the public that volunteer as trial participants – namely, that the aim of the research is to improve treatment of future patients.

The consequences of selective reporting can be disastrous. For example, several drug companies misrepresented the risk of harms with their cyclo-oxygenase-2 (COX-2) inhibitors, and the widespread use of rofecoxib has likely caused about 100,000 unnecessary heart attacks in the USA alone,[10,11] corresponding to about 10,000 deaths, which could have been avoided by using other, equally effective drugs causing less harm.

As another example, the effect of antidepressants was 32% larger in the published trials than in all trials that had been submitted to the US Food and Drug Administration.[7] When the UK National Institute for Health and Clinical Excellence (NICE) was drafting guidelines for the treatment of depression in children, they observed that, based on the published trials, they would recommend antidepressants, but based on all the trials, including the unpublished ones, they would not.[12] The companies had also concealed the fact that antidepressants increase the risk of suicide by coding suicidal events as something else, e.g. emotional lability, admission to hospital, lack of effect or drop-out, and by adding suicidal events to the placebo group, although the events happened in the run-in phase before patients were randomised.[4],[13]

Following the intervention of the European ombudsman, the European Medicines Agency (EMA) is now committed to providing access to clinical study reports and corresponding trial protocols.[2] Importantly, documents received by The Nordic Cochrane Centre have included individual patient data in anonymised format, identified by individual and test-centre numbers only. This allows for an independent assessment and coding of serious adverse events in a blinded fashion, which is expected to lead to much more reliable data on harms than those the drug companies have published.

However, access to data held by other agencies, including national ones, may still be challenging, or in some cases outright impossible. For example, although the United Kingdom acts as Reference Member State according to the Mutual Recognition Procedure in the European Union for the antidepressant drug fluoxetine, the UK Medicines and Healthcare products Regulatory Agency (MHRA) informed The Nordic Cochrane Centre on 25 May 2011 that it no longer holds the requested reports: "Under MHRA record management policy, all application files and data for licences are held for 15 years. After this period, files are destroyed unless there is a legal, regulatory, or business need to keep them, or unless they are considered to be of lasting historic interest."[14]

All data from all randomised clinical trials, including raw anonymised individual participant data that do not allow identification of individual participants, and the corresponding trial protocols to become publicly available free of charge and in easily accessible electronic formats;

Governments to consider introducing legislation that makes it a requirement to provide these data from all trials to the public within 12 months from the end of the randomised phase of the trial, in accordance with most international calls for data sharing;

Governments also to consider punitive measures for non-compliance; a requirement to continue to hold and make available core data indefinitely, or to pass such data to a central and accessible repository; and a recognition that ownership of trial data should be shared between sponsors, investigators and trial participants.

The Cochrane Collaboration recognises that the sharing of data from all clinical trials would lead to tremendous benefits for our societies for the following reasons: the current situation is harmful to patients and has been shown to lead to the avoidable death of tens of thousands of patients; we would become much better informed about the true benefits and harms of our interventions, which would lead to better treatment with fewer harms throughout health care; transparency would be increased, making it possible for independent scrutiny of the methods and the calculations reported in the trial publication compared with the trial protocol and the raw data, which would increase the likelihood that any malpractice was detected; the efficiency of healthcare research would be much improved, as many important research questions can be answered by using existing data, sparing researchers and patients from unnecessary, potentially dangerous and wasteful duplication of effort; and it would help identify healthcare strategies and uncertainties that require research, and to set priorities for research.

Declarations of interest

The author has completed the Unified Competing Interest form at www.icmje.org/coi_disclosure.pdf (available upon request) and declares (1) no receipt of payment or support in kind for any aspect of the article; (2) no financial relationships with any entities that have an interest related to the submitted work; (3) that the author/spouse/children have no financial relationships with entities that have an interest in the content of the article; and (4) that there are no other relationships or activities that could be perceived as having influenced, or giving the appearance of potentially influencing, what was written in the submitted work.